[Supplemental role of thrombospondin-1 in the diagnosis of prostate cancer].

OBJECTIVE: To employ enzyme-linked immunosorbent assay (ELISA) to measure the serum level of thrombospondin-1 (TSP-1) and analyze its diagnostic value for prostate cancer. METHODS: The serum levels of TSP-1 were measured by human TSP-1 ELISA kit in 50 patients with organ-confined prostate cancer (n = 22) and non-organ-confined prostate cancer (n = 28). And the subjects of benign prostatic hyperplasia (BPH, n = 20) and healthy controls (n = 16) were selected. RESULTS: The average serum concentration of TSP-1 was (200 ± 49) µg/L in prostate cancer group, (281 ± 53) µg/L in BPH group and (323 ± 56) µg/L in healthy control group. There were significant inter-group differences in the serum levels of TSP-1 (both P < 0.05). The average serum concentration of TSP-1 was (216 ± 34) µg/L in organ-confined prostate cancer (including stages I and II) and (188 ± 49) µg/L in non-organ-confined prostate cancer (including stages III and IV) respectively (P = 0.030). The level of TSP-1 was also correlated with Gleason score (r = -0.32, P = 0.023). However, the relationship between TSP-1 levels and lymph node metastasis remained elusive (P = 0.189). The diagnostic sensitivity and specificity of TSP-1 and prostate specific antigen (PSA) for prostate cancer were 72%, 90% and 64%, 70% respectively (both P < 0.05). The area under the receiver operating characteristic curve (ROC) of TSP-1 and PSA were 0.886 and 0.719 respectively (P = 0.028). CONCLUSION: As a relatively ideal predictor of prostate cancer, the serum concentration of TSP-1 can not only distinguish prostate cancer from BPH, but also correlate with tumor stage and Gleason grade.

[Clinical features on chromophobe renal cell carcinoma].

OBJECTIVES: To explore the clinical, pathological features and prognosis of patients with chromophobe renal cell carcinoma. METHODS: From January 1998 to January 2008, clinical data of 29 patients with chromophobe renal cell carcinoma including clinical manifestations, imaging examinations, treatment models, pTNM stages and follow-up results, were summarized to investigate its features and prognosis. RESULTS: All cases had no obvious clinical and preoperative imaging presentation. There were 23 patients underwent radical nephrectomy, and 6 cases underwent nephron sparing surgery. Postoperative pathological findings confirmed the diagnosis of chromophobe renal cell carcinoma. Macroscopically, the cut surface of the tumors were generally beige in color. Histologically, it showed polygonal chromophobe cells and small round eosinophilic cells with eccentric hyaline degeneration. These tumor cells had a clear and sharp membrane, lightly stained abundant cytoplasm with a fine reticular translucent pattern and irregular nuclei. And a perinuclear halo was often seen in these cells. Histochemically, the tumor cells generally show a diffuse and strong reaction for CK-8 with a negative expression of Vimentin. The pTNM stages of the tumor were as follows, pT1N0M0 in 11 cases, pT2N0M0 in 8 cases, pT3aN0M0 in 5 cases, pT1N1M0 in 3 cases, pT2N1M0 in 2 cases. Twenty-six cases of patients were followed up (24 to 144 months, with an average of 90 months), 3 cases died of cardio-cerebrovascular disease, and local recurrence involved in 6 cases with reoperation in 4 cases, as well as distant metastasis in 1 case. Twenty-one cases survived with tumor-free. The statistical results indicated that the survival rates of the patients with chromophobe renal cell carcinoma in five years and ten years were 83.9%, 77.9%, respectively, compared with renal cell carcinoma of the same stage 63.8% and 49.9% at the same periods, and there is no difference in the survival rate of five years (P > 0.05) but significant difference in that of ten years (P < 0.01). CONCLUSIONS: Chromophobe renal cell carcinoma is a morphologically uncommon subtype of renal cell carcinoma with the good prognosis. Definite diagnosis depends on its typical pathological feature. Radical nephrectomy is the first choice for the treatment of chromophobe renal cell carcinoma.

Rapamycin regulates Akt and ERK phosphorylation through mTORC1 and mTORC2 signaling pathways.

Numerous studies have shown that mammalian target of rapamycin (mTOR) inhibitor activates Akt signaling pathway via a negative feedback loop while inhibiting mTORC1 signaling. In this report, we focused on studying the role of mTORC1 and mTORC2 in rapamycin-mediated Akt and ERK phosphorylation, and the antitumor effect of rapamycin in cancer cells in combination with Akt and ERK inhibitors. Moreover, we analyzed the effect of mTORC1 and mTORC2 on regulating cell cycle progression. We found that low concentrations rapamycin increased Akt and ERK phosphorylation through a mTORC1-dependent mechanism because knockdowned raptor induced the activation of Akt and ERK, but higher doses of rapamycin inhibited Akt and ERK phosphorylation mainly via the mTORC2 signaling pathway because that the silencing of rictor led to the inhibition of Akt and ERK phosphorylation. We further showed that mTORC2 was tightly associated with the development of cell cycle through an Akt-dependent mechanism. Therefore, we combined PI3K and ERK inhibitors prevent rapamycin-induced Akt activation and enhanced antitumor effects of rapamycin. Collectively, we conclude that mTORC2 plays a much more important role than mTORC1 in rapamycin-mediated phosphorylation of Akt and ERK, and cotargeting AKT and ERK signaling may be a new strategy for enhancing the efficacy of rapamycin-based therapeutic approaches in cancer cells.